Schedule-induced polydipsia: Effect of water temperature, ambient temperature, and hypothalamic cooling.

Conducted 3 polydipsia experiments with a total of 26 female Sprague-Dawley rats, 6 of which were implanted with thermodes and thermistors and 2 of which were implanted with thermistors alone in the medial preoptic area or posterior hypothalamus. A cold (5.C) ambient temperature reduced the amount of water consumed by food-deprived Ss tested with a VI schedule of reinforcement, while a warm (30.C) ambient increased water intake. Response rate in the cold was twice that in a neutral temperature. A hot (38.C) ambient suppressed the rate of responding and drinking. Cooling the hypothalamus substantially reduced water intake in a neutral ambient temperature. Ambient temperature affected the volume of a drink but not the frequency of drinking, while hypothalamic cooling affected both volume and frequency. Water temperature had little effect on polydipsia although less cold water was consumed than warm water. It is concluded that schedule-induced polydipsia is a temperature-dependent phenomenon. (39 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioning following repeated exposure to MDMA in rats: Role in the maintenance of MDMA self-administration.

There has been some controversy in the literature concerning the ability of ±3,4 methylenedioxymethamphetamine (MDMA) to reinforce operant responding in rats. In the present study, operant responding maintained by intravenous MDMA infusions increased when the fixed ratio schedule was increased from 1 to 5, decreased when saline was substituted for MDMA, and increased again when MDMA was reintroduced. During self-administration training, each infusion of MDMA was paired with the illumination of a light stimulus. The role of the continued presentation of this drug-associated stimulus in operant responding was measured in groups of rats that had received comparable exposure (average 19 daily test sessions) to MDMA during training. When either the light stimulus or the drug infusion was omitted, operant responding decreased gradually over the 15-day test period following training. When both the light stimulus and the MDMA infusion were omitted, there was a dramatic decrease in operant responding that persisted for the entire 15-day test period. These findings suggest that cues associated with MDMA develop conditioned properties that might contribute to drug taking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Naltrexone: disposition, metabolism, and effects after acute and chronic dosing

The disposition of naltrexone during acute and chronic administration of 100-mg oral dose was studied in 4 subjects. Following an acute dose the mean (X) peak naltrexone plasma level was 43.6 +/- 29.9 ng/ml at 1 hr and for the major biotransformation product, beta-naltrexol, was 87.2 +/- 25.0 ng/ml at 2 hr. Twenty-four hours after the dose the X levels of naltrexone and beta-naltrexol declined to 2.1 +/- 0.47 and 17.6 +/- 5.0 ng/ml, respectively. Following chronic administration and X peak plasma levels of naltrexone and beta-naltrexol rose to 46.4 +/- 18.5 and 158.4 +/- 89.9 ng/ml at 1 hr, but by 24 hr both compounds declined to levels of the same order as in the acute state at 24 hr. Plasma levels of naltrexone and beta-naltrexol measured 24 hr after the daily doses of naltrexone throughout the study indicated that steady-state equilibrium was rapidly attained and that there was no accumulation of naltrexone and beta naltrexol in the plasma after chronic treatment on 100 mg oral doses. Biexponential kinetics were observed for naltrexone and beta-naltrexol in the first 24 hr. The half-life of naltrexone and beta-naltrexol decreased slightly from the acute to thechronic study from 10.3 +/- 3.3 to 9.7 +/- 1.1 hr and from 12.7 +/- 2.6 to 11.4 +/- 2.0 hr. The plasma levels of naltrexone declined slowly from 24 through 72 hr from 2.4 to 1.7 ng/ml, with an apparent half-life of 96 hr. The renal clearance data indicate that naltrexone is partially reabsorbed while beta naltrexol is actively secreted by the kidney. During acute and chronic naltrexone administration the mean fecal excretion was 2.1% and 3.6% while urinary excretion was 38% and 70% of the dose in a 24-hr period. Opiate antagonism to 25 mg heroin challenges was nearly complete through 48 hr after naltrexone. At 72 hr the objective responses reappeared to a greater extent than the subjective ones. Correlation coefficient (r) between naltrexone plasma levels and opiate antagonism was 0.91 and between individual half-life of naltrexone and opiate antagonism it was 0.99.     

Comparative effects of various naturally occurring cannabinoids on food, sucrose and water consumption by rats

The effects of intraperitoneally injected detla9-tetrahydrocannabinol (THC), cannabinol (CBN) and cannabidiol (CBD) were compared to d-amphetamine sulfate (d-AMP) on food and water consumption and intake of two different concentrations of sucrose solutions. Three groups of rats were given the following dietary regimens within a 6-hr feed period day: 1 - water and dry food; 2 - water, dry food and five percent sucrose solution; 3 - water, dry food and 20% sucrose solution. Food and water consumption were dramatically reduced by each test drug at feeding periods immediately following and in some instances up to 4 days after dosing in all 3 groups. However, sucrose consumption was much less affected by each cannabinoid, inidcating a preference for sweet calories, whereas d-AMP had an equal anorexic action on both food and sucrose consumption. These data suggest for the first time in rats that a preference for sweet calories occurs during an overall anorexic effect of THC, CBN and CBD.     

Small changes in ambient temperature cause large changes in 3,4-methylenedioxymethamphetamine (MDMA)-induced serotonin neurotoxicity and core body temperature in the rat

The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA) is a drug of abuse and has been shown to be neurotoxic to 5-HT terminals in many species. MDMA-engendered neurotoxicity has been shown to be affected by both ambient temperature and core body temperature. We now report that small (2 degreesC) changes in ambient temperature produce changes in core temperature in MDMA-treated rats, but the same changes in ambient temperature do not affect core temperature of saline-treated animals. Furthermore, increases in core temperature of MDMA-treated animals increase neurotoxicity. Rats were given MDMA (20 or 40 mg/kg) or saline and placed in an ambient temperature of 20, 22, 24, 26, 28, or 30 degreesC using a novel temperature measurement apparatus that controls ambient temperature +/-0.5 degrees C. Two weeks after MDMA treatment, the rats were killed, and regional 5-HT and 5-hydroxyindole acetic acid levels were analyzed as a measure of neurotoxicity. Rats treated with MDMA at 20 and 22 degrees C showed a hypothermic core temperature response. Treatment with MDMA at 28 and 30 degreesC produced a hyperthermic response. At ambient temperatures of 20-24 degrees C, neurotoxicity was not observed in the frontal cortex, somatosensory cortex, hippocampus, or striatum. At ambient temperatures of 26-30 degrees C, neurotoxicity was seen and correlated with core temperature in all regions examined. These data indicate that ambient temperature has a significant affect on MDMA neurotoxicity, core temperature, and thermoregulation in rats. This finding has implications on both the temperature dependence of the mechanism of MDMA neurotoxicity and human use because fatal hyperthermia is associated with MDMA use in humans.     

Thermoregulation in rats exposed perinatally to dioxin: core temperature stability to altered ambient temperature, behavioral thermoregulation, and febrile response to lipopolysaccharide

Recent studies have shown that perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) alters thermoregulatory function in adult rats and hamsters, indicated by a reduced body temperature during the animal's nocturnal phase. The present study was designed to assess the behavioral thermoregulation, ability to develop a fever, and thermoregulatory stability as a function of ambient temperature (Ta) in rats exposed perinatally to TCDD. Pregnant Long-Evans rats were exposed on gestational day (GD) 15 to 1 microg TCDD/kg (po). The male offspring were implanted with transmitters to monitor core temperature (Tc) and motor activity (MA). The 24-h pattern of core temperature was affected by TCDD exposure, characterized by a reduced nocturnal Tc. At some ages, the diurnal Tc of the TCDD group was elevated. This dysfunction in temperature regulation was most apparent at 7 and 11 mo of age. The 24-h pattern of MA was also altered by TCDD. The hypothermic effects of TCDD were most pronounced at cooler Ta values of 10 to 22 degrees C. In contrast, behavioral thermoregulation, assessed by measuring the selected Ta and Tc of rats in a temperature gradient, was unaffected by TCDD. The ability to develop a fever following administration of lipopolysaccharide (LPS) endotoxin (Escherichia coli; 50 microg/kg) was accentuated in the TCDD-treated animals. The data confirm a nocturnal hypothermia in rats prenatally exposed to TCDD. However, the normal behavioral regulation of Tc suggests that hypothalamic thermoregulatory centers are not permanently altered. The accentuated fever in TCDD animals shows possible functional alterations in the neuroimmune and/or thermoregulatory axes involved in fever.     

Chronopharmacological effects on nicotine repeated administration on heart rate, body temperature and locomotor activity circadian rhythms in rats

The aim of this study was to compare morning and evening repeated nicotine administration on the circadian rhythms of heart rate (H), body temperature (T) and locomotor activity (A) in unrestrained rats by using implanted radio-telemetry transmitters. The study was divided into three 7-day periods: a control period (P1), a treatment period (P2) and a recovery period (P3). During P2, four rats received nicotine (1mg.kg(-1)) subcutaneously at 09.00 h and four rats received nicotine in the same conditions at 21.00 h. For P1, P2 and P3, a power spectrum analysis was applied in order to determine the dominant period of rhythmicity. If H, T and A circadian rhythms were detected, the characteristics of these rhythms were determined by cosinor analysis, expressed as means+/-SEM and compared by ANOVA. Our results indicated: (1) a lack of detection of A circadian rhythm during P2 for the morning group while H and T circadian rhythms were detected for the morning and evening group whatever the period. (2) alterations of mesors, amplitudes and acrophases of H and T circadian rhythms for the morning and evening group during P2 and alterations of mesor, amplitude and acrophase of A circadian rhythm for the evening group. Furthermore these alterations were significantly different for the morning and evening group during P2. These results showed that the time of administration of nicotine differently affect H, T and A rhythms. The authors suggest that these effects can be mediated by central cholinergic and/or monoaminergic mechanisms.     

Vasopressin administration in the first month of life: effects of growth and water metabolism in hypothalamic diabetes insipidus rats

Rats homozygous for the mutant gene for diabetes insipidus (Brattleboro strain) are stunted in growth compared to rats heterozygous for the mutant gene and normal rats without the mutant gene. The hypothesis was tested that normal growth depends upon the presence of vasopressin. It was expected that replacement therapy of vasopressin rats homozygous for diabetes insipidus would make possible a normal growth rate similar to that of rats heterozygous for diabetes insipidus. Rats heterozygous and homozygous for diabetes insipidus were treated with 0.25 U (Days 0-9) and 0.5 U (Days 10-29) of vasopressin during the first month of life. During the treatment period, vasopressin significantly increased the urine osmolatities of the homozygous rats demonstrating the renal effectiveness of the vasopressin. The results showed that remedial vasopressin administration could not produce normal growth rates in homozygous rats and may be detrimental. Six weeks following vasopressin treatment, homozygous, diabetes insipidus rats which had received vasopressin had increased 24 hr water intakes and decreased urine osmolalities compared to control, homozygous rats, Heterozygous rats also had decreased urine osmolalities resulting from vasopressin six weeks after the cessation of vasopressin treatment.     

Alcohol consumption, water consumption, and emotionality in mice.

Tested 95 F2 mice for 1 mo. on a variety of tests of emotionality and activity. For a 2nd mo. Ss were given a choice of tap water of 10% ethanol for fluid consumption. 42 measures from emotionality testing were correlated with 30 readings of alcohol and 30 readings of water consumption. Abosolute consumption of alcohol and the relationship between emotionality and alcohol consumption increased over the 30-day period. 3 major shifts in the pattern of correlations over time were observed, suggesting a 3-stage theory of fluid consumption in the 2-choice situation. High alcohol consumption in the last stage, which accounted for most of the correlations, is related to a pattern of emotionality involving high activity, low freezing, and low emotional defecation. A construct of stress resistance is hypothesized to account for these relationships in conflict with classical drive-reduction theory. The 1st stage is considered to be more compatible with classical drive-reduction theory. An intermediate or transition stage is also involved with suggestions that this may be more complex for alcohol than water consumption. (27 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Time course of ethylene thiourea in maternal plasma, amniotic fluid and embryos in rats following single oral dosing

Ethylene thiourea (ETU) was administered once orally to pregnant rats on gestation day 12 at a dose of 200 mg/kg, and its concentration-time courses in the maternal plasma, amniotic fluid and embryos were investigated. The ETU concentrations in the maternal plasma and amniotic fluid reached the peak level about 2 hr after dosing, then declined gradually and had disappeared by 48 hr. In embryos, the concentration of ETU peaked at 30 min after dosing and disappeared at 48 hr. The prolonged exposure of the embryos to the high concentration of ETU in the amniotic fluid could be partially responsible for the teratogenic effect of ETU.     

Reduction of stimulus-bound food consumption in the rat following amphetamine administration.

Studied the effects of intraperitoneal administration of dextroamphetamine on stimulus-bound food consumption in 30 male sated rats. Lateral hypothalamic stimulation which resulted in feeding was either programed to occur at regular intervals or delivered by the S's response (self-stimulation). Stimulus-bound food intake was reduced by dextroamphetamine, 3.0 or 4.0 mg/kg dosages being sufficient to cause almost complete anorexia. Reflexive sniffing and chewing of food and self-stimulation behaviors were unaffected. Results indicate that amphetamine selectively interacts with the adrenergic feeding system of the lateral hypothalamus to produce an inhibition of food consumption. (17 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Airway responses in healthy and asthmatic subjects following exposure to low ambient air temperature

Agonist-activated Ca2+ entry is important in many biological responses such as secretion and cell growth(1,2). In nonexcitable cells which have no voltage-operated Ca2+ channels (VOCC), agonist-receptor interaction can trigger Ca2+ entry across the plasmalemma via several entry pathways(1-3) (Fig 1): (A) channels which are intrinsic structures of the receptor (receptor-operated channels), (B) channels which are coupled to receptors via a G-protein (G-protein-operated channels), (C) channels which are activated by some second messengers (second-messenger-operated channels), and (D) channels which open upon intracellular nonmitochondrial Ca2+ store depletion (Ca2+ release-activated channels) resulting from inositol 1, 4, 5-trisphosphate-induced Ca2+ release or inhibition of Ca2+ re-uptake (see next section). Ca2+ entry via the 4th type of channel, also known as "capacitative Ca2+ entry" (CCE)[4], has aroused much interest in the past decade because of its intriguing nature as retrograde signalling. In this brief review, we present the evidence for and the possible biochemical processes involved in CCE. We also discuss the use of 2 novel Ca2+ entry blockers: tetrandrine and SK&F 96365. Emphasis will be put on the human leukemic HL-60 cell line, a popular cell system for intracellular Ca2+ homeostasis studies and also a model the signal transduction of which we have been investigating during the past few years.     

Orogastric, hydrational, and behavioral controls of drinking following water deprivation in rats.

Studied drinking and its associated behaviors in 168 female Sprague-Dawley rats deprived of fluid for 8, 24, or 48 hrs. The behavior of Ss drinking water could be divided into 3 successive stages: (a) an initial intense burst of drinking that could not be easily disrupted; (b) intermittent drinking, often distinguished by the brief appearance of conflict behavior directed at the drinking spout; and (c) termination of drinking. Drinking stopped well before the fluid loss, reflected in a sizable extracellular deficit, was restored. Intake of water was terminated when serum hyponatremia and hypoosmolality (and presumably cellular overhydration) developed in temporal continguity with drinking. These and other considerations suggest that the cellular fluid phase exerts significant inhibitory as well as excitatory control over drinking. (42 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Brain and plasma levels of cocaine and benzoylecgonine in lead-expose and cadmium-exposed rats following acute or chronic intraperitoneal administration of cocaine

We have cloned a full length cDNA coding for the activin type IIB receptor (GactRIIB) from the goldfish ovary. GactRIIB shares 73 and 70% amino acid identity in the extracellular domain, and 78 and 80% identity in the intracellular domain with the type IIB receptors of the mouse and Xenopus respectively. The intracellular domain of GactRIIB contains two serine kinase consensus sequences, DFKSRN and GTRRYMAPE, in agreement with the reports in other vertebrates that serine/threonine phosphorylation is involved in activin signal transduction. The identity of GactRIIB was confirmed by transient expression in the COS cells followed by activin binding. Iodinated human activin A bound to the GactRIIB-transfected cells and the binding could be completely inhibited by unlabeled activin. Affinity labeling revealed a band of about 85 kDa, which is in agreement with the reported type II receptors in other vertebrates. Together with the fact that activin is expressed in the goldfish ovary, the cloning of activin receptors from the ovary suggests paracrine and autocrine roles for activin in the goldfish ovarian functions.     

Antifibrotic and hemodynamic effects of the early and chronic administration of octreotide in two models of liver fibrosis in rats

The aim of this study was to assess the effect of the early and chronic administration of octreotide in the prevention of hepatic fibrosis and portal hypertension (PHT). Two experimental models of liver fibrosis caused by bile duct ligation (BDL) or CCl4 were divided into 4 rat groups: sham, placebo, and octreotide (10 and 100 micrograms/kg twice daily, subcutaneously). Liver fibrosis was assessed by the area of fibrosis (image analysis), liver hydroxyproline and fibronectin mRNA contents, and serum hyaluronate. Systemic and splanchnic hemodynamic changes were also evaluated, including the splenorenal shunt blood flow by the transit-time ultrasound (TTU) technique. In both models, splenorenal shunt blood flow was significantly lower in the octreotide groups than in the placebo group (P <.05), while portal pressure was not significantly decreased. There was a significant decrease in fibrosis by octreotide in the CCl4 model only: area of fibrosis: 13.9% +/- 3.7% vs. 9.8% +/- 2.5% (P <.01), hydroxyproline: 1.8 +/- 0.6 vs. 1.3 +/- 0.4 mg/g wet liver (P <.05), respectively, placebo vs. octreotide 10 micrograms/kg. There was a significant correlation between the area of fibrosis and hydroxyproline liver content (r =.87 in the biliary model and r =.91 in the CCl4 model; P <.0001). The early and chronic administration of octreotide prevents the development of portocollateral blood flow without reducing portal pressure in two models of liver fibrosis and the development of liver fibrosis in the CCl4 model.